FTIDC is a novel, orally bioactive, highly potent and selective negative allosteric modulator/antagonist of metabotropic glutamate receptor (mGluR) 1 with anxiolytic and antipsychotic effects. It blocks mGlu1 and mGlu5 with IC50 of 5.8 and 6200 nM, respectively. It may have therapeutic value for both humans and animal models. In the absence of ligand, it also functions as an inverse agonist of the mGlu1 receptor (IC50 = 7 nM). FTIDC inhibits L-glutamate-induced increases in intracellular calcium in mGlu1-expressing CHO cells and shows no effect at group II/III mGlu receptors. In vivo, it shows anxiolytic and antipsychotic effects in addition to inhibiting nociceptive behavior.
Physicochemical Properties
| Molecular Formula | C18H23FN6O |
| Molecular Weight | 358.41322 |
| Exact Mass | 358.191 |
| Elemental Analysis | C, 60.32; H, 6.47; F, 5.30; N, 23.45; O, 4.46 |
| CAS # | 873551-53-2 |
| PubChem CID | 11245287 |
| Appearance | Solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 558.2±60.0 °C at 760 mmHg |
| Flash Point | 291.4±32.9 °C |
| Vapour Pressure | 0.0±1.5 mmHg at 25°C |
| Index of Refraction | 1.624 |
| LogP | 2.15 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 26 |
| Complexity | 542 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1C(N2C(C)=C(C3=CCN(C(N(C)C(C)C)=O)CC3)N=N2)=CC=CN=1 |
| InChi Key | CJTLKLBSIFQKNT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H23FN6O/c1-12(2)23(4)18(26)24-10-7-14(8-11-24)16-13(3)25(22-21-16)15-6-5-9-20-17(15)19/h5-7,9,12H,8,10-11H2,1-4H3 |
| Chemical Name | 4-[1-(2-fluoropyridin-3-yl)-5-methyltriazol-4-yl]-N-methyl-N-propan-2-yl-3,6-dihydro-2H-pyridine-1-carboxamide |
| Synonyms | FTIDC |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | mGluR1a ( IC50 = 5.8 nM ); mGlu5 ( IC50 = 6200 nM ) |
| ln Vitro | FTIDC has IC50 values of 5.8 nM, 5.8 nM, 3.1 nM, and 7.7 nM for human mGluR1a, rat mGluR1a, mouse mGluR1a, and human mGluR1b in CHO cells, respectively, indicating that it inhibits the increase in intracellular Ca2+ concentrations caused by L-glutamate[1]. |
| ln Vivo | FTIDC (i.p. or p.o.; 1-30 mg/kg) exhibits a statistically significant inhibitory effect on the duration of face-washing behavior elicited in a dose-dependent manner at doses of 10 and 30 mg/kg with i.p. and 30 mg/kg with p.o.[1]. |
| Animal Protocol |
Male CD1 (ICR) mice of 6-weeks-old 1, 3, 10, and 30 mg/kg I.p. or p.o. |
| References |
[1]. Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther . 2007 Jun;321(3):1144-53. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 100 mg/mL (~279.0 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7901 mL | 13.9505 mL | 27.9010 mL | |
| 5 mM | 0.5580 mL | 2.7901 mL | 5.5802 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7901 mL |